GPR49 molecule is a protein encoded by the ENSG00000139292 gene of human chromosome 12q12, and its amino acid sequence characteristics have revealed that it is a member of the LGR family (Leucine-rich GPCR family, hereinafter referred to as the LGR family), which is a hormone receptor family of G-protein coupled seven-transmembrane proteins (Non-patent Document 1). Members of the LGR family include hormone receptors such as LHR, TSHR, and FSH, as well as LGR7 and LGR8, ligands of which are relaxin, insulin-like peptide 3 (INSL3), and such (Non-patent Document 2). All ligands are known to comprise heterogeneous peptides, and mainly transmit signals via cAMP. The LGR family has a structure comprising a seven-transmembrane protein region and an N-terminal long extracellular region. In the extracellular region, there are 9 to 17 repeats of a leucine-rich region (leucine-rich repeat: LRR) comprising of 25 amino acids or so. GPR49 comprises 17 LRRs (Non-patent Document 1). According to analysis of TSHR and such, G-protein-coupled signal transduction occurs when a ligand binds to this extracellular LRR with high affinity, and also to the second extracellular loop region (Non-patent Document 3; Pharmacology & Therapeutics 103, 21 (2004)). The ligands of GPR49 have not yet been identified, but since ligands of DLGR2, a closely-related LGR of Drosophila, were found to be Bursicon comprising Burs and Pburs (partner of Bur) which are molecules of the BMP antagonist family, there are reports that the ligands of LGR4, LGR5 (GPR49), and LGR6 with yet unknown ligands may also be BMP antagonists (Non-patent Document 4 and Non-patent Document 2). As for the functions of these molecules, analyses of knockout mice have suggested that they are involved with ankyloglossia (ankylogenesis) (Non-patent Document 5). Furthermore, from gene expression analyses of hair follicle stem cells, they are speculated to be involved in the proliferation of stem cells (Non-patent Document 6).
With regard to involvement in cancer, Yamamoto et al. have reported that GPR49 is highly expressed in liver cell cancer patients (Non-patent Document 7), and also that expression of GPR49 at the mRNA level is upregulated particularly in patients with mutations in beta-catenin. Furthermore, Ito et al. have mentioned GPR49 as an example of a molecule highly expressed in gastric cancer patients based on Affymetrix Genechip data analyses (Patent Document 1).
It has been reported that expression of GPR49 is upregulated in colon cancer and ovarian cancer, and upregulation of expression at the mRNA level is observed at 64% (25/39) of colon cancer patients and 53% (18/33) of ovarian cancer patients (Non-patent Document 8). Immunostaining using PoAb has revealed that it is expressed in the normal tissues of placenta and skeletal muscles (Non-patent Document 8). As for its involvement with canceration, focus formation assay showed that NIH3T3 subjected to only gene transfer did not show focus formation in four weeks, but cells supplemented with a culture supernatant obtained from a SW620 culture (conditioned medium) showed focus formation within three weeks. Accordingly, GPR49 is assumed to induce ligand-dependent canceration. Accumulation of subG1 cells and apoptosis induction was observed in siRNA experiments. It is suggested that GPR49 may have functions of inhibiting apoptosis induction in colon cancer cells.
However, based on expression of cancer cell lines it has also been reported that although GPR49 expression is upregulated in colon cancer, ovarian cancer, glioma, and melanoma, such an upregulation is not seen in breast cancer and lung cancer (Non-patent Document 8).    [Patent Document 1] WO 2000/071710    [Non-patent Document 1] Mol. Endocrinology. 12, 1830 (1998)    [Non-patent Document 2] Journal of Endocrinology 187, 333 (2005)    [Non-patent Document 3] Pharmacology & Therapeutics 103, 21 (2004)    [Non-patent Document 4] PNAS 102, 2820 (2005)    [Non-patent Document 5] Molecular and Cellular Biology, 24, 9736 (2004)    [Non-patent Document 6] Nature Biotechnology 22, 411 (2004)    [Non-patent Document 7] Hepatology 37, 528 (2003)    [Non-patent Document 8] Cancer Biology & Therapy 5, 419 (2006)